Nkomo, Vuyisile T.

Abstract Aims Beat-to-beat variability in cycle length is well-known in atrial fibrillation (Afib); whether this also translates to variability in annulus size remains unknown. Defining annulus maximal size in Afib is critical for accurate selection of percutaneous devices given the frequent association with mitral and tricuspid valve diseases. Methods and results Images were obtained from 170 patients undergoing 3D echocardiography [100 (50 sinus rhythm (SR) and 50 Afib) for mitral annulus (MA) and 70 (35 SR and 35 Afib) for tricuspid annulus (TA)]. Images were analysed for differences in annular dynamics with a commercially available software. Number of cardiac cycles analysed was 567 in mitral valve and 346 in tricuspid valve. Median absolute difference in maximal MA area over four to six cycles was 1.8 cm2 (range 0.5–5.2 cm2) in Afib vs. 0.8 cm2 (range 0.1–2.9 cm2) in SR, P < 0.001. Maximal MA area was observed within 30–70% of the R-R interval in 81% of cardiac cycles in SR and in 73% of cycles in Afib. Median absolute difference in maximal TA area over four to six cycles was 1.4 cm2 (range 0.5–3.6 cm2) in Afib vs. 0.7 cm2 (range 0.3–1.7 cm2) in SR, P < 0.001. Maximal TA area was observed within 60–100% of the R-R interval in 81% of cardiac cycles in SR, but only in 49% of cycles in Afib. Conclusion MA and TA reach maximal size within a broad time interval centred around end-systole and end-diastole, respectively, with significant beat-to-beat variability. Afib leads to a larger beat-to-beat variability in both timing of occurrence and values of annulus size than in SR.

Abstract Background: Left atrial (LA) function can be impaired by the atrial fibrillation (AF) ablation and might be associated with the risk of recurrence. We sought to determine whether the post-procedural changes in LA function impact the risk of recurrence following AF ablation. Methods: We retrospectively reviewed patients who underwent AF ablation between 2009 and 2011 and underwent transthoracic echocardiography before ablation, 1-day and 3-month after ablation. Peak left atrial contraction strain (PACS) and left atrial emptying fraction (LAEF) were evaluated during sinus rhythm and compared across the three time points. The primary endpoint was atrial tachyarrhythmia recurrence after ablation. Results: Out of 144 patients were enrolled (mean age 61±11 years, 77% male, 46% persistent AF). PACS and LAEF initially decreased 1-day following ablation but partially recovered within 3 months in PAF patients, with a similar trend in the PerAF patients. After median 24 months follow-up, 68 (47%) patients had recurrence. Patients with recurrence had higher PACS1-day than that in non-recurrence subjects (-10.9±5.0%%vs. -13.4±4.7, p=0.003). PACS1-day -12% distinguished recurrence cases with a sensitivity of 67.7% and specificity of 60.5%. The Kaplan-Meier curves showed significant difference in 5-year cumulative probability of recurrence between those with PACS≥ -12 % and PACS < -12% (log rank p<0.0001). Multivariate regression showed that PACS1-day was an independent risk factor of arrhythmia recurrence. Conclusions: Left atrial function deteriorates immediately following AF ablation and partially recovers in 3 months but remains abnormal in the majority of patients. PACS1-day post procedure predicts arrhythmia recurrence at long-term follow-up.

Background Whether the poor outcomes of isolated tricuspid valve surgery are related to the operation itself or to certain patient characteristics including late referral is unknown. Methods and Results Adult patients who underwent isolated tricuspid valve surgery were identified in the Nationwide Readmissions Database (2016–2017). Patients who had redo tricuspid valve surgery, endocarditis, or congenital heart disease were excluded. Multivariable logistic regression was performed to identify contributors to postoperative mortality. A total of 1513 patients were included (mean age 55.7±16.6 years, 49.6% women). Surrogates of late referral were frequent: 41% of patients were admitted with decompensated heart failure, 44.3% had a nonelective surgery status, 16.8% had advanced liver disease, and 31% had an unplanned hospitalization in the prior 90 days. The operation was performed on day 0 to 1 of the hospitalization in only 50% of patients, and beyond day 10 in 22% of patients. In‐hospital mortality occurred in 8.7% of patients. Median length of stay was 14 days (7–35 days), and median cost was $87 223 ($43 122–$200 872). In multivariable logistic regression analysis, surrogates for late referrals (acute heart failure decompensation, nonelective surgery status, or advanced liver disease) were the strongest predictors of in‐hospital mortality (odds ratio [OR], 4.75; 95% CI, 2.74–8.25 [ P <0.001]). This was also consistent in a second model incorporating unplanned hospitalizations in the 90 days before surgery as a surrogate for late referral (OR, 5.50; 95% CI, 2.28–10.71 [ P <0.001]). Conclusions The poor outcomes of isolated tricuspid valve surgery may be largely explained by the late referral for intervention. Studies are needed to determine the role of early intervention for severe isolated tricuspid regurgitation.

Abstract Background There is a paucity of data about the prevalence and natural history of mitral annular calcification (MAC). Purposes In a large cohort of patients undergoing clinically-indicated echocardiography, we aimed to evaluate the prevalence and the natural history of MAC, and the frequency of associated mitral valve dysfunction (MVD). Methods Retrospective review of all patients who underwent echocardiographic evaluation at our institution between January 1st and December 31st 2015. The patients were stratified into 3 groups: MAC with MVD, MAC without MVD, no MAC. MVD was defined as moderate or greater mitral regurgitation (MR) or stenosis (MS). The 3 groups were compared for baseline clinical and echocardiographic characteristics and all-cause mortality during follow-up. Results Of 24,415 evaluated patients, 5478 (22%) had MAC. Patients with MAC were older (75±10 vs. 60±16 years, p&lt;0.01) and more often female (46% vs. 43%, p&lt;0.01). MVD was more frequently observed in patients with MAC (16% vs. 7%, p&lt;0.01); moderate or greater MR was found in 10% of patients with MAC vs. 6% without MAC (p&lt;0.01) and MS in 7% vs. 0.5% (p&lt;0.01). In patients with MAC, those with MVD were more often female and more frequently had creatinine ≥2mg/dl and moderate or greater aortic stenosis (AS) than those without MVD (Fig. A). Kaplan-Meier survivals at 1 year were 75% in patients with MAC and MVD, 87% in those with MAC without MVD, and 92% in those without MAC (Fig B). Adjusted for age, sex, diabetes, creatinine ≥2 mg/dl, coronary artery disease, left ventricular ejection fraction &lt;50%, and AS, MAC was associated with higher all-cause mortality (adjusted hazard ratio1.4, 95% confidence interval: 1.3–1.5, p&lt;0.01); combined MAC and MVD was associated with the highest mortality during follow-up of 2.5±1.8 years. Conclusion In a large cohort of patients undergoing echocardiographic evaluation, the prevalence of MAC was 22%. MV dysfunction was more than twice as prevalent in patients with MAC as without. Patients with MAC had higher all-cause mortality than patients without MAC. Among patients with MAC and mitral valvular dysfunction, adjusted mortality was two-fold higher compared to those without MAC. Funding Acknowledgement Type of funding source: None

Abstract Background Transmitral gradient (TMG) is highly dependent on hemodynamic state, leading to discordance between TMG and mitral valve area (MVA). The effect of heart rate (HR) and stroke volume (SV) on TMG among patients with mitral stenosis (MS) is poorly understood. Purposes We aimed to (1) develop a formula for projected TMG (proTMG) for assessment of MS severity under varying hemodynamics; (2) assess the prognostic value of proTMG in patients with MS. Methods All patients evaluated for suspected MS without ≥moderate other valve disorder at our tertiary center between 2001 and 2017 were analyzed. Projected TMG is the expected gradient under normal flow (SV 80–94 ml and HR 60–79 bpm), and was modeled based on the observed impact of HR and SV on TMG by multiple regression analysis. The data were randomly split (2:1) into training and testing sets. The improvement in agreement between MVA and proTMG was evaluated. Composite cardiac events including all-cause death and mitral valve interventions were compared according to TMG grade using TMG and proTMG. Severe and moderate MS were defined as MVA ≤1.5 cm2 and 1.5–2.0 cm2 respectively, by the continuity equation. MVA ≤1.0 cm2 was considered as very severe MS. Results Of 4973 patients with suspected MS (age 73±12 years, 33% male), severe MS was present in 437 (9%, including 98 with very severe MS) and moderate MS in 934 (19%). In 838 patients with normal HR and SV, very severe, severe and moderate MS corresponded to TMG ≥12 mmHg, ≥6 mmHg and 4–6 mmHg, respectively. In the training set (n=3315), the median [interquartile range] of HR and SV were 70 [61–80] bpm and 97 [83–113] mL in men (n=1120), and 72 [63–82] bpm and 84 [71–97] mL in women (n=2195), respectively. The impact of HR and SV on TMG for men and women were 0.07 and 0.08 mmHg per 1 bpm increase in HR (95% confidence interval [CI] 0.06–0.07 and 0.07–0.08), and 0.03 and 0.05 mmHg per 1 mL increase in SV (95% CI 0.03–0.03 and 0.04–0.05), respectively. Therefore, the final formula to calculate proTMG was: proTMG=TMG-0.07(HR-70)-0.03(SV-97) in men and proTMG=TMG-0.08(HR-72)-0.05(SV-84) in women. In the testing set (n=1658), the proTMG (kappa=0.63, 95% CI 0.60–0.66) had better agreement with MS severity by MVA than TMG (kappa=0.28, 95% CI 0.24–0.32). To explore the prevalence of patients reclassified using proTMG, in 98 with TMG ≥12 mmHg, proTMG remained ≥6 mmHg. Of 657 with TMG 6–12 mmHg, proTMG remained ≥6 mmHg in 356 (54%), and decreased to &lt;6 mmHg in 301 (46%). In patients with TMG 6–12 mmHg, proTMG ≥6 mmHg was associated with higher probability of cardiac events compared with &lt;6 mmHg during follow-up of 2.8±3.1 years (Figure). Conclusion We propose a novel concept of projected TMG defined as the expected transmitral gradient at normal HR and SV levels. This improved the diagnostic yield of Doppler TMG measurements for MS severity assessment and identified a low-risk subset of patients with elevated TMG due to high HR or SV. Funding Acknowledgement Type of funding source: None

Abstract Background Bicuspid aortic valve (BAV) is an important cause of AR; these patients belong to a young and male predominant population and are distinctively different from tricuspid aortic valve (TAV). However, the differences between BAV and TAV in AR have not been completely explored. Purpose To explore differences between patients with BAV and TAV in hemodynamically significant aortic regurgitation (AR). Methods Consecutive patients with ≥moderate-severe AR were retrospectively identified from 2006 to 2017. Results Of 798 patients (502 with TAV, mean age 67±14 years; 296 with BAV, mean age 46±14 years) followed for 6.1±3.6 years, 403 underwent AV surgery (AVS); 154 died during follow-up. BAV men (94%) tended to become symptomatic when left ventricle enlarged; TAV patients became symptomatic before left ventricular (LV) enlargement. During follow-up, BAV patients had lower mortality (hazard ratio [HR], 0.19; P&lt;0.0001) and higher incidence of AVS (HR, 1.28; P=0.01) than TAV, which attenuated after adjusted on age, sex, comorbidities, LV ejection fraction (LVEF), functional class, and time-dependent AVS. In a propensity-matched cohort, differences of survival and incidence of AVS between BAV and TAV were not demonstrated. After a median of 6.3 (IQR: 3.3–9.3) years, 53 patients died post-AVS; TAV patients having class I surgical triggers had poor survival than TAV-non-class I patients and BAV patients with and without class I triggers (Figure). Class I triggers had no effect on BAV patients regarding post-AVS survival. LVEF&lt;60% was associated with increased mortality in both TAV and BAV. Conclusions The correlation between larger LV size and symptomatic status only applied in BAV men. Patients with BAV and significant AR tended to have better survival and higher incidence of AVS, likely driven by inherent younger age and less comorbidity than patients with TAV. Class I surgical triggers had heavier negative impact on poor survival in TAV patients. The cutoff of LV dysfunction in AR may be LVEF 60%. Figure 1. Kaplan-Meier curves post-AVS Funding Acknowledgement Type of funding source: None

Objective To comprehensively explore contemporary differences between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) patients with chronic haemodynamically significant aortic regurgitation (AR). Methods Consecutive patients with chronic ≥moderate-severe AR from a tertiary referral centre (2006–2017) were included. All-cause mortality, surgical indications and aortic valve surgery (AVS) were analysed. Results Of 798 patients (296 BAV-AR, age 46±14 years; 502 TAV-AR, age 67±14 years, p<0.0001) followed for 5.5 (IQR: 2.9–9.2) years, 403 underwent AVS (repair in 96) and 154 died during follow-up. The 8-year AVS incidence was 60%±3% versus 53%±3% for BAV-AR and TAV-AR, respectively (p=0.014). The unadjusted (real-life) 8-year total survival was 93%±7% versus 71%±2% for BAV-AR and TAV-AR, respectively (p<0.0001), and became statistically insignificant after sole adjustment for age (p=0.14). The within-group relative risk of death in BAV-AR patients demonstrated a large age-dependent increase (two fold at 50–55 years, up to 10-fold at 70 years). The presence of baseline symptoms was significantly associated with death for both BAV-AR (p=0.039) and TAV-AR (p<0.0001), but the strength of the association decreased with age adjustment for BAV-AR (age-adjusted HR 2.43 (0.92–6.39), p=0.07) and not for TAV-AR (age-adjusted HR, 2.3 (1.6–3.3), p<0.0001). As compared with general population, TAV-AR exhibited baseline excess risk which further increased at left ventricular ejection fraction (LVEF) <60% and left ventricular end-systolic dimension index (LVESDi) >20 mm/m2; similar thresholds were observed for BAV-AR patients. Conclusion BAV-AR patients were two decades younger than TAV-AR and underwent AVS more frequently, resulting in a considerable real-life survival advantage for BAV-AR that was determined primarily by age and not valve anatomy. Pragmatically, regardless of valve anatomy, patients with haemodynamically significant AR and age >50–55 years require a low-threshold for surgical referral to prevent symptom development where LVEF <60% and LVESDi >20 mm/m2 seem appropriate referral thresholds.

AbstractObjectivesThe aim of this study was to assess the 30 day incidence of paravalvular leak (PVL) and need for aortic valve reintervention of a fourth generation balloon expandable transcatheter valve with enhanced skirt (4G‐BEV) (SAPIEN 3 Ultra) compared with a third generation balloon expandable transcatheter valve (3G‐BEV) (SAPIEN 3).BackgroundThe incidence of PVL has steadily declined with iterative improvements in transcatheter aortic valve replacement (TAVR) technology and implantation strategies.MethodsPatients who underwent TAVR at Mayo Clinic from 7/2018 to 7/2019 were included in a prospective institutional registry. 4G‐BEV has been utilized since 2/2019, and, after this date, 3G‐BEV and 4G‐BEV were simultaneously used. 4G‐BEV had three sizes (20, 23, and 26 mm) while 3G‐BEV included four sizes (20, 23, 26, and 29 mm). Both cohorts were evaluated at 30 days post‐TAVR with a transthoracic echocardiogram to assess for PVL.ResultsA total of 260 consecutive patients were included. Of these, 101 patients received a 4G‐BEV and 159 patients received a 3G‐BEV. There were more females (p = .0005) and a lower aortic valve calcium score (p = .02) in the 4G‐BEV cohort at baseline. Age, STS risk score, NYHA Class, and aortic valve mean gradient did not differ between groups. 4G‐BEV was associated with a lower incidence of mild PVL (10.8 vs. 36.5%; p < .0001) and moderate PVL (0 vs. 5.8%) compared to the 3G‐BEV at 30 days. There was no association between PVL and valve size in either cohort.ConclusionsUtilization of 4G‐BEV is associated with reduced PVL at 30 days post‐TAVR compared with 3G‐BEV.

Abstract Aims Chronic volume-overload can impair systolic and diastolic myocardial properties. We tested the hypothesis that Intrinsic Cardiac Elastography may detect alterations in passive myocardial elasticity in patients with chronic severe mitral regurgitation (MR) and predict worsening left ventricular (LV) function after mitral valve repair (MVr). Methods and results Comprehensive transthoracic echocardiography and cardiac elastography were performed in 80 patients with primary MR (prolapse and/or flail leaflets) of varying severity and compared with 40 normal subjects. In patients who underwent MVr (n = 51), elastography measurements were related to changes in left ventricular ejection fraction (LVEF) at short-term (3–4 days post-op) and mid-term (1 year) follow-up. Most patients were asymptomatic or mildly symptomatic and had preserved LVEF (&gt;60%). Intrinsic velocity propagation (iVP) of myocardial stretch, a direct measure of myocardial stiffness, was higher in patients with severe MR {median 2.0 [interquartile range (IQR) 1.5–2.2] m/s, range 1.1–3.4 m/s; n = 56} compared to normal subjects [median 1.7 (IQR 1.5–1.8) m/s; n = 40; P = 0.0005], but not in those with mild or moderate MR [median 1.7 (IQR 1.4–1.9) m/s; n = 24]. A higher iVP was associated with more severe LV volume-overload and LV and left atrial enlargement (P &lt; 0.05 for all). In patients undergoing MVr, a higher iVP independently predicted a larger drop in LVEF post-intervention (short-term, P = 0.001; 1 year, P = 0.007), incrementally to pre-operative LVEF (P &lt; 0.05). Conclusion Non-invasive measurements of myocardial stiffness were able to predict functional deterioration after MVr for chronic primary MR. Further studies should investigate the mechanisms and practical utility of this novel measurement.

Background: Left ventricular global longitudinal strain (GLS) is associated with long-term outcomes of patients with severe aortic stenosis. However, its prognostic value in patients with moderate aortic stenosis remains unknown. Methods: Patients diagnosed with moderate aortic stenosis (1.0< aortic valve area ≤1.5 cm 2 ) and left ventricular ejection fraction ≥50% were identified. GLS was assessed by 2-dimensional strain imaging using speckle-tracking method. All-cause mortality was assessed according to the median GLS value. Results: Two hundred eighty-seven patients were included (median age 76 years; 47% male). Mean aortic valve area was 1.25 cm 2 , left ventricular ejection fraction 62%, and median GLS −15.2%. During a median follow-up of 3.9 years, there were 103 deaths (36%). Mortality was higher in patients with GLS>−15.2% (hazard ratio 2.62 [95% CI 1.69–4.06]) compared with patients with GLS ≤−15.2% even after adjusting for confounders. Mortality rates at 1, 3, 5 years were 21%, 35%, 48%, respectively, in patients with GLS >−15.2%, and 6%, 15%, 19% in those with GLS ≤−15.2%. Even among those with left ventricular ejection fraction ≥60%, GLS discriminated higher-risk patients ( P =0.0003). During follow-up, 106 (37%) patients underwent aortic valve replacement with median waiting-time of 2.4 years, and their survival was better than patients without aortic valve replacement. Among those patients undergoing aortic valve replacement, prognosis was still worse in patients with GLS >−15.2% ( P =0.04). Mortality rates at 1, 3, 5 years were 2%, 10%, 20%, respectively, in patients with GLS >-15.2% and 2%, 5%, 6% in those with GLS ≤−15.2%. Conclusions: Impaired GLS in moderate aortic stenosis patients is associated with higher mortality rates even among those undergoing aortic valve replacement.